52 results about "2-Azetidinone" patented technology

The invention encompasses (3R,4S)-4-((4-benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)-2-azetidinone (Compound 2a) having an enantiomeric purity of at least about 97.5%. The invention also encompasses Compound 2a having a chemical purity of at least about 97%. The invention further encompasses processes for preparing Compound 2a from Compound 1 having the following formula: The invention also encompasses processes for preparing a compound having the following formula: from a compound having the following formula: wherein R is selected from the group consisting of: H or a hydroxyl protecting group. The invention also encompasses processes for preparing Compound 2a, preferably to form Compound 2a-Form 01. Also included are processes for preparing ezetimibe from Compound 2a-Form 01 or Compound 2a prepared according to the invention, compositions containing such ezetimibe, and methods for reducing cholesterol using such compositions.

The present invention provides 4-substituted-2-azetidinone compounds, bicyclic 2-5-diketopiperazine compounds, and pharmaceutical compositions thereof that are potent, safe and effective neuroprotective agents. Due to their strong central nervous system (CNS) activity, the compounds can be used to enhance memory and to treat a variety of neurological disorders. The compounds are particularly useful for treating neurological disorders caused by, or associated with, CNS trauma.

The invention discloses a process for synthesizing 4-acetoxy-2-azetidinone. Epoxy butyrate is used as raw material with 1,4-2((oxo-propyl) amino) benzene to generate (2R, 3R)-1, 4-2((N-oxo-propyl-N-2, 3-epoxy butyl) amino) benzene which closes ring under the effect of potassium carbonate to get (3R, 4R)-1, 4-2((-3-((1'-R-hydroxide radical) ethide)-4-acetyl-2-azetidinone-1-radical) benzene of three chiral centers; benzoyl hydroperoxide is added to have a reaction to obtain (3R, 4R)-1, 4-2((-3-((1'-R-hydroxide radical) ethide)-4-acetoxy-2-azetidinone-1-radical) benzene; compound (3R, 4R)-1, 4-2((-3-((1'-R-tert-butyl dimethyl silica) ethide)-4-acetoxy-2-azetidinone-1-radical) benzene is obtained by tert-butyl dimethyl chlorosilane protection; and finally, (3R, 4R)-4-acetoxy-3-((1'-R-tert-butyl dimethyl silica) ethide)-2-azetidinone is obtained through ozone oxidation and protecting group removal. The method has simple raw material, moderate reaction condition, environmental friendliness,and can be applied to large scale industrialization production.

A method for the preparation of (S)-alcohol oxazolidides of general formula II, in which PG represents hydrogen or a hydroxyl protecting group, such as trimethylsilyl, tert-butyldimethylsilyl, benzyloxycarbonyl, tert-butoxycarbonyl, benzyl, benzhydryl or trityl, in which a ketal oxazolidide of general formula III, where PG has the same meaning as above and R means an alkyl with 1-4 carbon atoms, linear or branched, such as methyl, ethyl, isopropyl or butyl, or R+R together represents a divalent alkyl, or substituted with 1 or 2 alkyl groups, e.g. 1,2-ethylene, 1,2-propylene, 1,2-butylene, 1,3-propylene or 2,2-dimethyl-1,3-propylene, is deprotected by the action of acidic reagents in a mixture of water and a water-miscible solvent in the temperature range of 0 to 100° C. (stage A), and the obtained ketone oxazolidide of general IV, in which PG has the same meaning as above, is reduced with asymmetrical reagents in an inert organic solvent in the temperature range of −30 to +40° C. (stage B).

A process for producing a compound represented by the following formula (II) which comprises treating a compound represented by the following formula (I) (wherein R1, R2 and R3 represent each a specific substituent) with an enzyme capable of asymmetrically hydrolyzing an ester and the novel compound (II). The process of the present invention makes it possible to easily obtain an optically active 2-azetidinone derivative in a large amount at a low cost

The invention discloses a novel technical method for synthesizing ezetimibe (a compound 1), and belongs to the field of organic chemical medical synthesis. The method comprises the following steps: synthesizing a (3R, 4S)beta-lactam ring of a key intermediate (a compound 9) by taking p-anisaldehyde, 4-fluoroaniline and glutaric anhydride as main raw materials; and reducing and hydrolyzing the compound to obtain ezetimibe. The method disclosed by the invention adopts simply and easily-available materials, and is less in synthesis steps, and stable in process; a chiral four-membered ring of the key intermediate is directly constructed by virtue of one-step reaction to obtain an important intermediate (3R, 4S)-1-(4- fluorophenyl)-3-[(3S)-3-]4-fluorophenyl)-3-carbonyl propyl]-4-(4-methoxypheyl)-2-azetidinone (a compound 9); a target enantiomer proportion in the product is high, post-treatment operation is simple, and industrial large-scale production is easy to realize.

The invention encompasses (3R,4S)-4-((4-benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)-2-azetidinone (Compound 2a) having an enantiomeric purity of at least about 97.5%. The invention also encompasses Compound 2a having a chemical purity of at least about 97%. The invention further encompasses processes for preparing Compound 2a from Compound 1 having the following formula:The invention also encompasses processes for preparing a compound having the following formula:from a compound having the following formula:wherein R is selected from the group consisting of: H or a hydroxyl protecting group. The invention also encompasses processes for preparing Compound 2a, preferably to form Compound 2a-Form 01. Also included are processes for preparing ezetimibe from Compound 2a-Form 01 or Compound 2a prepared according to the invention, compositions containing such ezetimibe, and methods for reducing cholesterol using such compositions

The present invention relates to a process for preparing (3R,4S)-3-[[[R]-1′-t-butyldimethylsilyloxy]ethyl]-4-[(R)-1″-carboxyethyl]-2-azetidinone (beta-methylazetidin-2-one; 4-BMA), a key intermediate for the synthesis of carbapenem and penem antibiotics. Specifically, the present invention relates to a process comprising first, the preparation of a chiral auxiliary from cheap L-Phenylalaninol, and then the preparation of 4-BMA in high yield and high selectivity, under industrially mild condition.

An industrially easily realizable and economical process comprising only few steps, and built on new intermediates for the production of 1-(4-3(R)-[3(S)-(4-fluorophenyl)-3-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone (ezetimibe) according to the reaction scheme described herein.

The instant invention provides novel cholesterol absorption inhibitors of Formula I and the pharmaceutically acceptable salts and esters thereof. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating and preventing atherosclerosis and atherosclerotic disease events.

A process for the production of 1-(4-3(R)-[3(S)-(4-fluorophenyl)-3-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone (ezetimibe) according to the following reaction scheme: (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) where the substances of the general Formulas II, IV, VI, VIII, IX, X and XI are new, Formula III is a non-isolated intermediate, R1, R2 and R3 are represented by the compounds of Formulas Va-Vd, (Va), (Vb), (Vc), (Vd) and R4 is a silyl, e.g., tert-butyl-dimethyl-silyl, tert-butyl-diphenyl-silyl group.

The invention relates to a synthesis method of a (3R, 4R)-3-[(R)-1-tertiary butyl dimethyl Si-O-ethyl]-4-acetoxyl-2-azetidinone derivative. The derivative is prepared by carrying out a reflux reaction on 4-AA at 30-120 DEG C in an organic solvent by using zinc powder as a catalyst. Compared with the traditional beta-lactam antibiotic derivative using a larger group, the invention has the advantages that a smaller group easier to obtain is used for synthesizing the beta-lactam antibiotic derivative in the method, and the synthesis method has high activity, good selectivity and high atom economy. Raw materials used in the reaction have low toxicity and are easy to obtain, and a heavy metal catalyst is not needed to be used, which is safe and has no influence on subsequent pharmaceutical synthesis. The method has simple process, easy operation and moderate reaction condition.

The invention discloses a method for synthesizing 2-azetidinone in the technical field of chemical synthesis. The method comprises specific steps as follows: S1, preparation of a mixed solution; S2, addition of an aid and dilution; S3, solution extraction and drying; S4, addition of sodium hydroxide and heating; S5, solution neutralization, water washing and drying; S6, toluene dissolution; S7, detection with a chromatograph; S8, product purification treatment. The synthesis method is simple, the prepared finished product has high accuracy, the temperature and the reaction time are controllable in the synthesis process, no raw material waste phenomenon is caused in the synthesis process and the method is suitable for large-scale production in a factory.

A synthesis method of 4-acetoxyl-2-azetidinone comprises the following steps of: (1) taking N-p-methoxypheny-N-(acetyl) methyleneimine as a raw material and carrying out cyclization reaction with (R)3-tert-butyldimethylsilyloxy-sulfo-butyrate-S-2-pyridinyl ester to obtain (3S,4S)-3-[(1'R)-tert-butyldimethylsilyloxyethyl]-4-acetyl-1-p-methoxyphenyl-2-azetidinone; (2) preparing (3R,4R)-3-[(1'R)-tert-butyldimethylsilyloxyethyl]-4-acetoxyl -1-p-methoxyphenyl-2-azetidinone from peroxyacetic acid through oxidization in the presence of Na3PO4 and a phase transfer catalyst; and (3) removing protective groups to obtain a final product (3R,4R)-3-[(1'R)-tert-butyldimethylsilyloxyethyl]-4-acetoxyl-2-azetidinone. The invention has the advantages of shortening reaction period, improving reaction total yield, and improving reaction yield and product purity by introducing the phase transfer catalyst in the step (2). The method is simple, causes small pollution and has great application value and economic benefit.

The invention relates to a preparation method of 4-acetyloxy-2-azetidinone compounds, and is used for solving the problem that the large-scale industrial production cannot be favorably realized because of defects such as severe reaction condition, complex treatment process, high cost, serious environment pollution and the like in the prior art. The method provided by the invention comprises the step of carrying out oxidization deacidification in the existence of a dehydrating agent N, N'-dicyclohexylcarbodiimide and an oxidizing agent peroxyacetic acid by taking 4-carboxyl-2-azetidinone compounds I as raw materials to obtain the 4-acetyloxy-2-azetidinone compounds II. A heavy metal oxidizing agent or catalyst is prevented from being used in the oxidization deacidification process, so that the residue and discharge of heavy metals and environmental pollution caused by the heavy metals are greatly reduced. Byproducts generated in a reaction process can be conveniently recycled, so that the production cost is reduced to the great extent, and the preparation method is more excellent on the aspect of economical efficiency. The method is mild in reaction condition, simple and convenient to operate and suitable for large-scale production; the 4-acetyloxy-2-azetidinone compounds are easy to separate and purify and high in yield.